Inhibitors of gastric acid secretion functioning by antagonism of the histamine H2-receptor are effective antiulcer agents. Structurally, such compounds are typically viewed as molecules having three substituents or fragments; i.e., A-B-C, each of which can independently affect the antisecretory activity. The "A" portion may be a substituted or unsubstituted aromatic or heteroaromatic group such as are disclosed in, for example, U.S. Pat. No. 3,950,333 to Durant et. al., U.S. Pat. No. 4,128,658 to Price et. al., and Belgian Patents 867,106 and 875,846 (Derwent Abstracts 84065A/47 and 79110B/44, respectively).
The central, or "B" portion, may be a connecting chain joined to A such as A--CH.sub.2 SCH.sub.2 CH.sub.2 --, AOCH.sub.2 CH.sub.2 CH.sub.2, and the like.
The remaining terminal substituent "C" is structurally distinct from either the A or B portions and may be, for example, a substituted guanidine, a substituted 1,1-diamino ethylene, or a 3,5-diamino-1-alkyl triazole as disclosed in the aforementioned U.S. Patents to Durant et. al., and Price et. al., as well as in Belgian Patent 875,846.
The present invention is directed to unique "C" moieties which confer antisecretory activity when combined with the A-B molecular fragments comprising these antiulcer agents. These novel "C" moieties, i.e., 3,4-diaminoisothiazole-1-oxides and -1,1-dioxides, when incorporated into the A-B molecular fragments, afford compounds that exhibit gastric antisecretory activity comparable to or greater than known prior art compounds, including those disclosed in the above-identified U.S., Belgian and European patents. The disclosure of 4-isothiazolin-3-one-1-oxides and -1,1-dioxides in U.S. Pat. No. 4,062,859 does not teach or suggest how to synthesize the novel compounds of this invention as no appropriate precursors nor amine displacement reactions are disclosed.